Increased bone resorption by osteoclast-specific deletion of the sodium/calcium exchanger isoform 1 (NCX1)

Pflugers Arch. 2017 Feb;469(2):225-233. doi: 10.1007/s00424-016-1923-5. Epub 2016 Dec 9.


Calcium is a key component of the bone mineral hydroxyapatite. During osteoclast-mediated bone resorption, hydroxyapatite is dissolved and significant quantities of calcium are released. Several calcium transport systems have previously been identified in osteoclasts, including members of the sodium/calcium exchanger (NCX) family. Expression pattern and physiological role of NCX isoforms in osteoclasts, however, remain largely unknown at the moment. Our data indicate that all three NCX isoforms (NCX1, NCX2, and NCX3) are present in murine osteoclasts. RANKL-induced differentiation of murine osteoclast precursors into mature osteoclasts significantly attenuated the expression of NCX1, while NCX2 and NCX3 expressions were largely unaffected. To study the role of NCX1 during osteoclast differentiation and bone resorption, we crossed mice with exon 11 of the NCX1 gene flanked by loxP sites with cathepsin K-Cre transgenic mice. Mature osteoclasts derived from transgenic mice exhibited an 80-90% reduction of NCX1 protein. In vitro studies indicate that NCX1 is dispensable for osteoclast differentiation, but NCX1-deficient osteoclasts exhibited increased resorptive activity. In line with these in vitro findings, mice with an osteoclast-targeted deletion of the NCX1 gene locus displayed an age-dependent loss of bone mass. Thus, in summary, our data reveal NCX1 as a regulator of osteoclast-mediated bone resorption.

Keywords: Bone; NCX1; Osteoclast; Sodium/calcium exchanger.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption / genetics
  • Bone Resorption / metabolism*
  • Calcium / metabolism
  • Cell Differentiation / physiology
  • Cell Line
  • Ion Transport / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Osteoclasts / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RANK Ligand / metabolism
  • Sequence Deletion / genetics
  • Sodium / metabolism
  • Sodium-Calcium Exchanger / genetics*
  • Sodium-Calcium Exchanger / metabolism*


  • NCX1 protein, mouse
  • Protein Isoforms
  • RANK Ligand
  • Sodium-Calcium Exchanger
  • Sodium
  • Calcium